The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial.

ABSTRACT: CDK4/6 inhibition with endocrine therapy is now a standard of care for advanced estrogen receptor-positive breast cancer. Mechanisms of CDK4/6 inhibitor resistance have been described preclinically, with limited evidence from clinical samples. We conducted paired baseline and end-of-treatment circulating tumor DNA sequencing from 195 patients in the PALOMA-3 randomized phase III trial of palbociclib plus fulvestrant versus placebo plus fulvestrant. We show that clonal evolution occurs frequently during treatment, reflecting substantial subclonal complexity in breast cancer that has progressed after prior endocrine therapy. RB1 mutations emerged only in the palbociclib plus fulvestrant arm and in a minority of patients (6/127, 4.7%, P = 0.041). New driver mutations emerged in

SUBMITTER: O'Leary B 

PROVIDER: S-EPMC6368247 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature